Institution
Division of Reproductive Biology, Department of Biochemistry, Johns Hopkins
University, School of Hygiene and Public Health, 615 North Wolfe Street,
Baltimore, MD 21205, USA.
Title
Long-term suppression of Leydig cell steroidogenesis
prevents Leydig cell aging.
Source
Proceedings of the National Academy of Sciences of the United States of
America. 96(26):14877-81, 1999 Dec 21.
Abstract
Male aging is accompanied by reduced testosterone production
by the Leydig cells, the
testosterone-producing cells of the testis. The mechanism by
which this occurs is unknown. Based on the observations that reactive oxygen
is capable of damaging components of the steroidogenic pathway and that
reactive oxygen is produced during steroidogenesis itself, we hypothesized
that long-term suppression of steroidogenesis might inhibit or prevent
age-related deficits in Leydig cell
testosterone production. To test this, we administered
contraceptive doses of testosterone to groups of young (3
months old) and middle-aged (13 months old) Brown Norway rats via Silastic
implants to suppress endogenous Leydig cell
testosterone production. After 8 months, the implants were
removed, which rapidly (days) restores the ability of the previously
suppressed Leydig cells to produce
testosterone. Two months after removing the implants, when
the rats of the two groups were 13 and 23 months of age, respectively, the
Leydig cells in both cases were found to produce
testosterone at the high levels of young
Leydig cells, whereas significantly lower levels were
produced by the 23-month-old controls. Thus, by placing the
Leydig cells in a state of steroidogenic "hibernation," the
reductions in Leydig cell testosterone
production that invariably accompany aging did not occur. If hormonal
contraception in the human functions the same way, the adverse consequences
of reduced testosterone in later life (osteoporosis, reduced
muscle mass, reduced libido, mood swings, etc. ) might be delayed or
prevented.